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Intrapallidal injection of botulinum toxin A recovers gait deficits in a parkinsonian rodent model
Author(s) -
Tsang Adrianna R.,
Rajakumar Nagalingam,
Jog Mandar S.
Publication year - 2019
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13230
Subject(s) - subthalamic nucleus , globus pallidus , basal ganglia , glutamatergic , deep brain stimulation , neuroscience , parkinson's disease , medicine , psychology , glutamate receptor , central nervous system , disease , receptor
Aim Modulation of electrical activity in the subthalamic nucleus has been therapeutically effective in Parkinson's disease. Pharmacological manipulation of glutamate release from subthalamic neurons could also favourably alter basal ganglia activity to improve motor symptoms. This study investigates the efficacy of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the globus pallidus internal segment by botulinum toxin A (BoNT‐A) in a parkinsonian model. Methods Unilateral 6‐hydroxydopamine lesioned parkinsonian rodents and controls received microinfusions of BoNT‐A or vehicle into the ipsilateral internal globus pallidus (n = 8 per group). Changes in gait were measured by the CatWalk apparatus, along with assessment of apomorphine‐induced rotational behaviour prior to and following BoNT‐A injection. Immunofluorescent staining for markers of glutamatergic, GABAergic and total terminals was performed at the internal globus pallidus. Results Administration of a single dose of BoNT‐A (0.5 ng) significantly improved the rotational asymmetry and gait abnormalities. Ameliorations in speed, body speed variation, cadence and walking pattern were comparable to pre‐lesioned animals, and persisted up to 1 month following BoNT‐A injection. These changes are associated to BoNT‐A's ability to selectively target glutamatergic terminals. Conclusion Blockade of subthalamic hyperactivity by BoNT‐A leads to sufficient reorganization in the basal ganglia needed to generate a consistent rhythmic pattern of walking. This suggests the potential use of intracerebral BoNT‐A to produce effective neuromodulation in the parkinsonian brain, as well as expansion into other neurodegenerative disorders linked to excitotoxity.